Modeling and docking antibody structures with Rosetta

We describe Rosetta-based computational protocols for predicting the three-dimensional structure of an antibody from sequence and then docking the antibody-protein-antigen complexes. Antibody modeling leverages canonical loop conformations to graft large segments from experimentally-determined structures as well as (1) energetic calculations to minimize loops, (2) docking methodology to refine the VL-VH relative orientation, and (3) de novo prediction of the elusive complementarity determining region (CDR) H3 loop. To alleviate model uncertainty, antibody-antigen docking resamples CDR loop conformations and can use multiple models to represent an ensemble of conformations for the antibody, the antigen or both. These protocols can be run fully-automated via the ROSIE web server or manually on a computer with user control of individual steps. For best results, the protocol requires roughly 2,500 CPU-hours for antibody modeling and 250 CPU-hours for antibody-antigen docking. Tasks can be completed in under a day by using public supercomputers.